Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle

作者：Mohammad Alqudah, Rima Abdul Razzak, Mahmoud A. Alfaqih, Othman Al‐Shboul, Ahmed Al‐Dwairi, Safa Taha · 发表于：International Journal of Molecular Sciences · 年份：2022 · DOI：10.3390/ijms24010441 · 被引用次数：11 · 研究领域：Neuroendocrine regulation and behavior、Neuroscience of respiration and sleep、Infant Health and Development

Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP3) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10−7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10−9–10−5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with th...